In fields that use the materials described above, various kinds of synthetic or natural macromolecular materials have been utilized in assorted configurations. Medical materials in which the raw materials are biogenic portions from equine, swine and bovine sources have also been used. All such medical materials made by conventional techniques comprise materials that are heterologous or foreign to the human body. Consequently, such medical materials manufactured by conventional techniques are unable to eliminate completely the undesirable effects such as immune reaction and reaction to foreign body.
There is a medical material made of freeze-dried dura mater encephali, a connective tissue membrane, collected from human cadaver specimens. The freeze-dried dura mater encephali is the only homologous medical material that has been approved as wound filler for replacement. However, in recent years, serious side effects and concerns such as that of prion, a pathogen of transmissible Creutzfeldt-Jakob syndrome, have been pointed out, as this medical material contains cellular substances such as epithelial and fibroblast layers of connective tissue membrane.
Moreover, there are also medical materials made of natural or synthetic macromolecular or polymeric materials, and medical materials for implants in which the raw material is equine or bovine pericardium that is completely modified chemically with glutaraldehyde, having nearly the same characteristics as synthetic macromolecular materials which are insoluble, non-degradable and non-absorbable in the body. Such medical materials, when implanted in the body, become encapsulated with endothelium. Such encapsulation is a physiologic phenomenon of self defense in response to the foreign body. The capsule thickens and becomes hypertrophic with time, remaining in the body permanently. This is an abnormal phenomenon for the body and causes naturally incoherence and imbalance in existence and growth between the implant site and surrounding normal tissues, possibly causing untoward results.
Since January, Showa 58 (1983), the present inventors and/or their collaborators have conducted studies on the technique and applied for various patents. Such techniques are described below.
Japanese Patent No. 1641621 is concerned with a medical material of membranous or tubular configuration for prosthesis for bladder, urethra and ureter. The medical material is made of composite materials of natural or synthetic macromolecular fiber and human amnion. This medical material failed to achieve complete antigenic or allergic biocompatibility and had the drawback of being non-degradable and insoluble, remaining in the body as a foreign body.
Unexamined Japanese Patent Publication Hei No. 7-116242 (i.e., 116242/95) is concerned with a medical material comprising two collagenous membranes and a mesh-like intermediate material inbetween, glued together with an adhesive. Namely this medical material is a composite substance comprising collagen-like membranes and an intermediate mesh-like material of synthetic fiber. The "collagen-like membrane" described here includes silicon membrane, gelatin membrane, other natural macromolecular gel membrane and synthetic macromolecular gel membrane. Therefore that term is not a scientifically well-accepted term but is a very indefinite term. In addition, the membrane retains the foreign-body reaction characteristic of synthetic fiber.
Unexamined Japanese Patent Publication Hei No. 7-213597 (i.e., 213597/95), published Aug. 13, 1995, discloses a purified collagen-like substance. The "purified collagen-like substance" used in Example 1, described in the specification was stated clearly as "a compact layer of human amnion". The patent is concerned with a twisted thread made of the compact layer of the human amnion, with medical materials made of the twisted thread and with manufacturing methods of the thread and the medical materials. The technique disclosed in the patent had a drawback of lacking physical strength, as physical strength depended on cross-linking density solely between collagen molecules in the substrate material.
As described above, existing medical materials are found to cause some concerns to the body and/or to have insufficient physical conditions required in surgical maneuvers. In the present invention, it is attempted to provide a safe, effective and useful medical material, i.e., an ultimately ideal medical material. The ultimately ideal medical material for treatment used in the surgical field is one that simultaneously satisfies safety, effectiveness and usefulness listed below.
(1) Safety: devices for implant that are used for treating bones or tissues and remain in contact with the body for a long period of time (30 days or longer) must be proven safe in tests for cytotoxicity, sensitization, subacute toxicity, implantation and others according to methods established in the International Organization for Standardization (ISO). Furthermore, laws require that each device must be proven for prescribed safety based on safety criteria in wide-ranged chemical, physical and biological tests according to the provisions. The ISO guideline of safety for surface-contacting devices has lists of tests, methods and evaluation criteria that are classified by contact sites; skin, mucous membrane and damaged surface, and require to prove the safety. In addition, devices must meet safety criteria determined by the laws. Medical devices originating from biological tissues must be proven completely safe, in addition to all of the above, from medical risk of pathogens including virus and bacteria which are the infectious pathogens of hepatitis (types A, B and C), HIV or venereal disease and prion which is a transmissible pathogen of Creutzfeldt-Jakob syndrome.
(2) Effectiveness of medical devices used as wound prosthesis or dressing: unless physiological function in addition to physical and mechanical function is satisfactory, the medical material is not recognized as being ultimately ideal. The ultimately ideal conditions for the physical and mechanical functions are that the medical materials applied to defective lesions can be used satisfactorily in any technique; adhesion with adhesives, manual and mechanical sutures, and the material can adhere and fix the normal tissues and organs after defective lesions are resected and removed. The material also must have properties that are consistent with physical and mechanical functions of normal tissues and organs.
The ultimately ideal conditions of physiological function described above must simultaneously satisfy the conditions listed below.
(1) Medical material should be a homologous material.
(2) Surgical sites of the body are replaced with normal tissues as medical materials decompose and are absorbed under ideal conditions as time passes.
(3) Oozing and leakage of blood and body fluid and leakage of gas are inhibited at surgical sites.
(4) Drainage is unnecessary.
(5) Materials have ideal qualities and physical and mechanical strength.
(6) Surgical technique is made easier, surgical time is shortened and early cure is made possible.
The scientific principles explaining the condition (1) and (2) described above can be summarized as following. The science of the connective tissue has established theory of principles regarding "cell proliferation and extracellular matrix" and "damage healing and extracellular matrix". It is a scientific principle regarding physiological mechanism of the body in which damaged sites self-repair as tissue is formed by cell proliferation. The connective tissue is composed with laminated layers of, in order, epithelium layer, basement membrane layer, compact layer and fibroblast layer. The mechanism of formation of connective tissue is thought to be that specific cells for the connective tissue are taken into the compact layer. As the taken cell proliferates, other layers are formed in succession, making connective tissue. Essential conditions for cell proliferation are said to be the ideal matrix, formed by collagen fiber that is made up with various collagens which constitute the compact layer, and cell growth factor substances. According to this scientific principle, a medical material that satisfies the ultimately ideal condition of physiological function is a homologous medical material that preserves the matrix of the compact layer which comprises various types of human collagen which constitutes human connective tissue.
(3) Usefulness: medical material should be developed for patients and for advancement and improvement of medical welfare. That is to say that the ultimately ideal medical material is one with usefulness that satisfies conditions of early healing of diseases, early discharge of patients, shortened surgical time (usefulness to surgeons), stable quantity of supply (fairness of welfare), long-term stability of quality standard and reasonable cost.
In light of the ideal conditions described above that the ultimately ideal medical material must possess, medical materials made with conventional technique have those fundamental and essential defects listed below.
(1) Medical materials of natural or synthetic macromolecular materials or medical materials, such as implants made of raw material of equine or swine pericardium that is completely modified chemically with glutaraldehyde to be insolvable, non-degradable and non-absorbable characteristics nearly similar to that of synthetic macromolecules, are capsulated with endothelium. The capsulation is due to physiological phenomenon of self-defence response to a foreign body. The capsule thickens and becomes hypertrophic with time, remaining in the body permanently. Such an abnormal phenomenon for the body causes naturally incoherence and imbalance in existence and growth between the implant site and surrounding normal tissues. The materials do not eliminate the risk of developing inconvenient situation.
(2) Freeze-dried dura mater encephali, that has been approved and marketed as a homologous wound prosthesis for replacement is made of raw material of dura mater encephali collected from human cadaver, does not eliminate medical risk caused by transmissible pathogen prion and unstable quantity of supply as well as high cost.
(3) Medical materials marketed currently as wound dressings include swine skin, plastic film, non-woven fabric of alginic acid fiber and other various products. All these products leave keloid or scar at the treated sites and require renewal more than once during the healing period. They are mere substitutes until the ultimately ideal wound dressing appears.
(4) There is medical material made of type I collagen that is extracted and purified from corium of bovine or swine skin, and then telopeptide is removed. Medical materials made of such collagen also are not free from following defects; industrial means and technique are unable to eliminate antigenicity completely, physiological function of tissue regeneration is lacking, as the extracellular matrix which is considered to be the essential condition for regeneration of connective tissue is not formed, the material is a synthetic macromolecular compound which is completely modified chemically with glutaraldehyde and the like, and is physiologically analogous to plastic and the risks caused by slow virus such as AIDS virus and transmissible pathogens prion. The material is also a mere substitute.
(5) As a medical material that possesses degradability and absorbability in the body, suture made of animal intestine exists. The suture has the problems of persistent pathogens as with the collagen described above and of residual keloid and scar formation. Thread of polyglycolic acid (PGA) is marketed as degradable and absorbable suture, PGA mesh and non-woven fabric. The PGA thread, however, has persistent problems of carbohydrate-caused allergy and irritation.
It is attempted in the present invention to develop a medical material that will solve all problems caused by various factors remaining in existing techniques and satisfy the ultimate ideal conditions.